Significance of r-and K-selection in hematological malignancies

Research Project

Project/Area Number	13671051
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Hematology
Research Institution	THE UNIVERSITY OF TOKYO
Principal Investigator	MOTOKURA Toru FACULTY OF MEDICINE, Lecturer, 医学部附属病院, 講師 (00192823)
Project Period (FY)	2001 – 2002
Project Status	Completed (Fiscal Year 2002)
Budget Amount *help	¥3,100,000 (Direct Cost: ¥3,100,000) Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000) Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywords	multistep oncogenesis / r-selection / K-selection / p-glycoprotein / multidrug resistance / ARF / p53
Research Abstract	By using an SRB assay and a clonogenic assay, we found the emergence of multidrug resistance (MDR) phenotype after K-selection of EJ-ras and c-myc-transformed rat embryo fibroblasts, MR5 and MR8 cells. RT-PCR analysis of expression of drug resistance-related genes suggested the involvement of ABC transporters such as p-glycoprotein/MDR1, MRP1 and BCRP. FACS analysis of doxorubicin intracellular accumulation indicated the augmented P-glycoprotein function in K-selected cells. In order to clarify the molecular mechanisms for refractory disease, we are trying to establish a Burkitt leukemia model for r- and K-selection by using EBV and c-myc oncogene transduction, and also trying to clone target genes which confer tumor cells growth advantages under K-selection by using an retroviral expression cloning system.